Ubiquitin-proteasome system modulates zygotic genome activation in early mouse embryos and influences full-term development

• Published in: Journal of Reproduction and Development Vol. 64; no. 1; pp. 65 - 74
• Main Authors: HIGUCHI, Chika, SHIMIZU, Natsumi, SHIN, Seung-Wook, MORITA, Kohtaro, NAGAI, Kouhei, ANZAI, Masayuki, KATO, Hiromi, MITANI, Tasuku, YAMAGATA, Kazuo, HOSOI, Yoshihiko, MIYAMOTO, Kei, MATSUMOTO, Kazuya
• Format: Journal Article
• Language: English
• Published: Tokyo THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT 2018; Japan Science and Technology Agency; The Society for Reproduction and Development
• Subjects: DNA-directed RNA polymerase; Embryos; Genomes; Maternal-to-zygotic transition; Original; Proteasome inhibitors; Proteasomes; RNA polymerase; Transcription; Ubiquitin; Ubiquitin-proteasome system; Zygotic genome activation
• ISSN: 0916-8818; 1348-4400
• DOI: 10.1262/jrd.2017-127

Maternal RNA/protein degradation and zygotic genome activation (ZGA), occurring during maternal-to-zygotic transition (MZT), are the first essential events for the development of pre-implantation embryos. Previously, we have shown the importance of the ubiquitin-proteasome system (UPS) for initiation of minor ZGA at the 1-cell stage of mouse embryos. However, little is known about the mechanism of involvement of the UPS-degraded maternal proteins in ZGA. In this study, we investigated the effect of inhibiting maternal protein degradation by the reversible proteasome inhibitor, MG132, on post-implantation development and ZGA regulation during early cleavage stages. Our study revealed that zygotic transcription by RNA polymerase II (Pol II) at the 1-cell stage was delayed and the full-term development was affected by transient proteasome inhibition during 1 to 9 h post-insemination (hpi). Furthermore, we found that the transient inhibition of proteasome activity at the 2-cell stage delayed the onset of transcription of some major ZGA genes. These results support the model hypothesizing the requirement of sequential degradation of maternal proteins by UPS for the proper onset of ZGA and normal progression of MZT in early mouse embryos.